PLVAP

protein-coding

plasmalemma vesicle associated protein

Gene summary

Predicted to enable identical protein binding activity. Involved in MAPK cascade; positive regulation of cellular extravasation; and tumor necrosis factor-mediated signaling pathway. Located in caveola and cell surface. Implicated in congenital diarrhea. [provided by Alliance of Genome Resources, Jul 2025]

MANE transcript

NM_031310.3

Inheritance

ClinVar variants

P:9U:117B:118

Top phenotype

Diarrhea 10, protein-losing enteropathy type

gnomAD constraint

pLI —, LoF o/e 0.6

Max pathogenic AF

—

Genomic locus

chr19:17,351,450-17,377,342

External References & Databases

Ensembl (ENSG00000130300)

Transcript & Mutation Effects

hg38 • Region Span ~25.9 kb

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GenCC Phenotypes & Disease Associations

Curated gene-disease validity assertions and inheritance patterns

diarrhea 10, protein-losing enteropathy typeMODERATE

Inheritance Pattern: AR

Disease ID:MONDO:0032586

Submitter: Ambry Genetics

diarrhea 10, protein-losing enteropathy typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032586

Submitter: PanelApp Australia

congenital diarrhea 7 with exudative enteropathySUPPORTIVE

Inheritance Pattern: AR

Disease ID:MONDO:0014375

Submitter: Orphanet

diarrhea 10, protein-losing enteropathy typeSTRONG

Inheritance Pattern: AR

Disease ID:MONDO:0032586

Submitter: Labcorp Genetics (formerly Invitae)

Clinical Genomic Database (CGD)

Diarrhea 10, protein-losing enteropathy typeAR

Manifestation: Craniofacial; Gastrointestinal; Genitourinary

Intervention: Gastrointestinal

Rationale: The condition can involve severe protein-losing enteropathy, and awareness may allow early diagnosis and management (eg, with low-fat diet and middle-chain triglyceride-rich formula) which has been reported as beneficial in some individuals

Refs: 26207260; 29661969; 29875123

Source: CGD (NHGRI)

ClinVar Associated Diseases & Phenotypes

Reported disease conditions connected to PLVAP variants in ClinVar

7 Conditions Cataloged

not providedTotal: 205

Inborn genetic diseasesTotal: 87

PLVAP-related disorderTotal: 14

Diarrhea 10, protein-losing enteropathy typeTotal: 9

not specifiedTotal: 5

Paediatric disordersTotal: 1

See casesTotal: 1

ClinVar Variants & Pathogenicity by Type

Statistics based on transcript NM_031310.3. Only rare variants are included.

We include only reliable ClinVar variants with their consequences to MANE Select, MANE Plus Clinical transcripts, or transcripts with TSL equal to 1. Click a count to filter the variants table below.

Slight differences between displayed counts and ClinVar may occur due to a different transcript/consequence chosen by our variant effect predictor, or because we classify Benign/Likely benign as Likely benign and Pathogenic/Likely pathogenic as Likely pathogenic.

Effect	PathogenicP	Likely pathogenicLP	VUS	Likely benignLB	BenignB	Sum
synonymous			3 clinvar	91 clinvar	6 clinvar	100
missense	1 clinvar		112 clinvar	19 clinvar	2 clinvar	134
nonsense	3 clinvar					3
start loss						0
frameshift	2 clinvar	3 clinvar				5
splice donor/acceptor (+/-2bp)			2 clinvar			2
Total	6	3	117	110	8	244

Highest pathogenic variant AF is 0.000006160156

Loading ClinVar variants...

Transcript Catalog

Annotated transcript isoforms across RefSeq and Ensembl databases

Showing 4 of 16 transcripts

Transcript ID	Source	Protein ID	Coding Exons	MANE Status
NM_031310.3	RefSeq	NP_112600.1	6	MANE Select
ENST00000252590.9	Ensembl	ENSP00000252590.3	6	MANE Select
ENST00000595816.1	Ensembl	ENSP00000469369.1	3	Standard
ENST00000599426.1	Ensembl	ENSP00000472928.1	4	Standard

Gene Ontology (GO) Annotations & Pathways

Biological processes, molecular functions, cellular components and pathways

Biological Process

MAPK cascade
positive regulation of cellular extravasation
tumor necrosis factor-mediated signaling pathway
protein kinase C signaling

Molecular Function

protein binding
protein homodimerization activity

Cellular Component

caveola
cell surface
integral component of membrane
perinuclear region of cytoplasm
extracellular exosome

gnomAD Constraint

Source: gnomAD

Gene type: protein_coding
Transcript type: protein_coding
Transcript: ENST00000252590
Coding exons: 6
Length: 25903
Individuals with no LoFs: 125724
Homozygous LoFs: 0
Heterozygous LoFs: 23
Defined: 125747
p: 0.0000915

	Z-Score	Observed	Expected	Observed/Expected	Mutation Rate	Total Possible
Missense	0.549	267	293	0.910	0.0000195	2900
Missense (PolyPhen)		95	109.39	0.86843		1094
Synonymous	-0.984	133	119	1.11	0.00000762	872
Loss of Function	1.66	12	20.0	0.600	0.00000104	213

Population LoF Frequency

Population	CAF	p-value	Status
African	0	0.0	absent
Latino/Admixed American	0.00017	0.00017	rare
Ashkenazi Jewish	0	0.0	absent
East Asian	0.00011	0.00011	rare
Finnish	0.000092	0.000092	rare
European (Non-Finnish)	0.000088	0.000088	rare
South Asian	0.000065	0.000065	rare
Other	0.00016	0.00016	rare

dbNSFP Gene Annotations

Source: dbNSFP

Function: FUNCTION: Involved in the formation of stomatal and fenestral diaphragms of caveolae. May function in microvascular permeability. {ECO:0000269|PubMed:15155804}.;

Recessive Scores

pRec: 0.130

Intolerance Scores

RVIS EVS: -0.57
RVIS percentile EVS: 18.9

Essentials

Essential (CRISPR): N
Essential (CRISPR2): N
Essential (gene trap): N
Indispensability pred.: N
Indispensability score: 0.328

Gene Damage Prediction

	All	Recessive	Dominant
Mendelian	Medium	Medium	Medium
Primary Immunodeficiency	Medium	Medium	Medium
Cancer	Medium	Medium	Medium